抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

One of the most pervasive problems afflicting people throughout the world is inadequate access to clean water and sanitation. Problems with water are expected to grow worse in the coming decades, with water scarcity occurring globally, even in regions currently considered water-rich. Addressing these problems calls out for a tremendous amount of research to be conducted to identify robust new methods of purifying water at lower cost and with less energy, while at the same time minimizing the use of chemicals and impact on the environment. Here we highlight some of the science and technology being developed to improve the disinfection and decontamination of water, as well as efforts to increase water supplies through the safe re-use of wastewater and efficient desalination of sea and brackish water.

Science and technology for water purification in the coming decades

(2000). El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders: Vol. 1, No. 5, pp. 293-299.

El Escorial revisited : revised criteria for the diagnosis of amyotrophic lateral sclerosis

Laboratory Features Elevation of sarcoplasmic enzymes in serum (creatine phosphokinase, aldolase, transaminases and lactic dehydrogenase) is valuable both for diagnosis and for following the clinic...

Polymyositis and dermatomyositis (first of two parts)

http://experimentationlab.berkeley.edu/sites/default/files/AFMImages/butt_AFM.pdf

Force measurements with the atomic force microscope: Technique, interpretation and applications

Preface Part I. Overview of Pathologic and Pathogenic Comparison Between Sporadic Inclusion-Body Myositis and Hereditary Inclusion-Body Myopathies: 1. Newest approaches to diagnosis and pathogenesis of sporadic inclusion-body myositis and hereditary inclusion-body myopathies, including molecular-pathologic similarities to Alzheimer disease Part II. Historical Perspective: 2: Evolving concepts of inclusion-body myositis Part III. Sporadic Inclusion-Body Myositis - Clinical and Diagnostic Considerations: 3: Sporadic inclusion-body myositis: Clinical and laboratory features and diagnostic criteria 4: Inclusion-body myositis: natural history 5: Uncommon clinico-pathological forms of sporadic inclusion-body myositis: Report of four cases 6: Inclusion-body myositis: pathological changes 7: Unusual pathological forms of inclusion-body myositis, and neuromuscular disorders with IBM-like changes 8: Electrophysiological findings in inclusion-body myositis 9: Genetic factors in sporadic inclusion-body myositis Part IV. Hereditary Inclusion-Body Myopathies - Clinical and Diagnostic Considerations: 10: Hereditary inclusion-body myopathy in Jews of Persian origin: Clinical and laboratory data 11. Hereditary inclusion-body myopathy (h-IBM) with quadriceps sparing: epidemiology and genetics 12: Familial autosomal-recessive inclusion-body myositis with asymptomatic leukoencephalopathy 13: Welander distal myopathy - clinical, pathophysiological, and molecular aspects 14. Tibial muscular dystrophy - clinical, genetic, and morphological characteristics 15. Distal myopathy with rimmed vacuoles, inclusion-body myositis and related disorders in Japan 16. Inclusion-body myopathies 17. Is the muscle fiber in inclusion body-myositis an antigen-presenting cell of an innocent bystander? 18. Viruses, immunodeficiency and inclusion-body myositis 19. Myonuclear abnormalities may play a central role in the pathogenesis of muscle fiber damage in inclusion-body myositis 20. Nuclear degeneration and rimmed vacuole formation in neuromuscular disorders 21. Mitochondrial alterations in sporadic inclusion-body myositis 22. mtDNA analysis in muscle of patients with sporadic inclusion-body myopathy Part V. Treatment: 23. Evaluation of treatment for sporadic inclusion-body myositis 24. Personal experience in treating sporadic inclusion-body myositis Subject index.

Inclusion body myositis and myopathies.

In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial sites of accumulation. Monoclonal antibodies reactive for B cells, T cells, T cell subsets, killer (K) or natural killer (NK) cells, and the Ia antigen were used for cell typing. Macrophages were identified by the acid phosphatase reaction. Few extravascular mononuclear cells occurred in normal muscle. In all inflammatory myopathies, a mixed exudate of T cells, B cells, and macrophages was present. Mature K/NK cells were rare in all diseases. In dermatomyositis, polymyositis, and inclusion body myositis, there was a positive gradient for T cells, T8+ cells, and activated T cells and a negative gradient for B cells and T4+ cells between perivascular and endomysial sites. In scleroderma the predominant perimysial exudate consisted mostly of T cells and macrophages. The percentage of B cells at all sites, and the T4+/T cell ratio in the endomysium, were significantly higher in dermatomyositis than in the other diseases. In polymyositis and inclusion body myositis, the endomysial exudate contained a large number of T cells, T8+ cells, and activated T cells but only sparse B cells. T cells accompanied by macrophages focally surrounded and invaded nonnecrotic fibers in polymyositis and inclusion body myositis. Rare fibers in Duchenne dystrophy and a very few fibers in dermatomyositis and scleroderma were similarly affected. We infer that (1) T-B, T-T, and T-macrophage cooperativities are likely to exist in muscle in different myopathies; (2) T cell-mediated fiber injury plays a role in polymyositis and inclusion body myositis; (3) T cell-mediated fiber injury can also occur in inherited diseases, such as Duchenne dystrophy; and (4) a local humoral response may occur in muscle in dermatomyositis and possibly in polymyositis and inclusion body myositis.

Monoclonal antibody analysis of mononuclear cells in myopathies. I : Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells

Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic fibres, and an autoaggressive endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle specimens. All three of these features were present in 88% of the specimens. Electron microscopy confirmed the presence of filamentous inclusions in 40 of 43 patients. The inclusions are typically near vacuoles and a minimum of three vacuolated fibres must be scrutinized to detect them with confidence. There is no electromyographic pattern that can reliably distinguish IBM from other inflammatory myopathies. The typical clinical features in the patients diagnosed by histological criteria as IBM were: insidious onset after age 50 yrs with painless, proximal lower extremity weakness; slow but relentless progression with selectively severe involvement of quadriceps, iliopsoas, tibialis anterior, biceps and triceps muscles; relatively early depression of the knee reflexes; and a normal or mildly elevated serum creatine kinase level. The male: female ratio was 3:1. Distal weakness occurred in about 50%, but only in 35% was it as great or greater than proximal weakness. Significant associated illnesses include other autoimmune disorders (15%), diabetes mellitus (20%), and diffuse peripheral neuropathy (18%). Prednisone treatment at dose levels frequently effective in polymyositis failed to prevent disease progression in those patients observed for 2 or more years. Our findings support the notion that IBM is a distinct entity in which a set of pathological features is associated with a constellation of clinical findings.

Inclusion body myositis. Observations in 40 patients.

Throughout the nervous system, moment-to-moment communication relies on postsynaptic receptors to detect neurotransmitters and change the membrane potential. For the Cys-loop superfamily of receptors, recent structural data have catalysed a leap in our understanding of the three steps of chemical-to-electrical transduction: neurotransmitter binding, communication between the binding site and the barrier to ions, and opening and closing of the barrier. The emerging insights might be expected to explain how mutations of receptors cause neurological disease, but the opposite is generally true. Namely, analyses of disease-causing mutations have clarified receptor structure-function relationships as well as mechanisms governing the postsynaptic response.

Recent advances in Cys-loop receptor structure and function.

In a rare myopathy muscle fibers contained myriad lipid-filled vacuoles. Homogenates of the patient's muscle oxidized fatty acids more slowly than normal (11 controls). Addition of carnitine increased the oxidation rate with the patient's muscle to the level attained by the controls with carnitine. In five separate muscle samples from the patient the mean carnitine level was less than 20 percent of that observed in 42 controls. Carnitine palmityl transferase and palmityl thiokinase levels in the patient's muscles were not depressed. The present case represents the first recognized instance of carnitine deficiency in human skeletal muscle.

https://science.sciencemag.org/content/sci/179/4076/899.full.pdf

Andrew G. Engel

Papers

Inclusion body myositis and myopathies.

Monoclonal antibody analysis of mononuclear cells in myopathies. I : Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells

Inclusion body myositis. Observations in 40 patients.

Recent advances in Cys-loop receptor structure and function.

Carnitine Deficiency of Human Skeletal Muscle with Associated Lipid Storage Myopathy: A New Syndrome